Impact of time from symptom onset to diagnosis in infective endocarditis: insights from the nationwide NIDUS registry

Background Infective endocarditis (IE) often presents with non-specific symptoms, which may delay diagnosis and treatment. Previous studies exploring symptom duration and timing of diagnosis have been limited by small cohorts or single-centre studies. Purpose To investigate patient characteristics, microbial aetiology, treatment, and all-cause mortality of patients with IE in relation to symptom duration prior to diagnosis. Methods We included all patients with first-time IE in Denmark from 2016 to 2021 using data from the NatIonal Danish Endocarditis StUdies (NIDUS) registry. Only patients with left-sided IE and available symptom duration data were included. Patients were stratified according to symptom duration prior to diagnosis into three groups: short (≤7 days), intermediate (8–29 days), and prolonged (≥30 days). We compared patient characteristics and clinical presentation across groups. The primary outcome was six-month mortality. Results A total of 2,938 patients with left-sided IE were included. The median symptom duration was 8 days, and 517 (17.6%) patients had symptoms ≥30 days. Patients with symptom duration ≤7 days compared with those with ≥30 days were older (median 74.1 vs. 72.2 years), more often female (35.1% vs. 24.8%), and had more comorbidities. The short-duration group compared with the prolonged-duration group had a higher prevalence of embolism (14.5% vs 8.9%), sepsis (28.2% vs. 12.2%) and Staphylococcus aureus bacteraemia (38.3% vs. 11.6%), but a lower prevalence of Streptococcus spp. (31.0% vs. 38.9%) and Enterococcus spp. (12.0% vs. 23.4%). The short-duration group more often presented with fever but less often with myalgia, dyspnoea, and significant weight loss. The short- and intermediate-duration groups underwent surgery less-frequently (18.1% and 23.2%) than the prolonged-duration group (31.7%). Large vegetations (>10 mm) were the most frequent indication for surgery overall, particularly in the prolonged-duration group, whereas Class I indication were more prevalent in short- and intermediate-duration groups. In-hospital mortality did not differ between groups. The six-month cumulative incidence of mortality was significantly lower in the prolonged-duration group (21.8%), while the short- and intermediate-duration groups had similar cumulative incidences, (28.7%) and (28.9%), respectively (Figure). However, after multivariable adjustment, symptom duration ≥30 days (vs. ≤7 days) was not associated with significantly different mortality. (adjusted hazard ratio 0.92 [95% CI: 0.74-1.14]). Conclusion In this nationwide study of patients with left-sided IE, short symptom duration prior to diagnosis was associated with more virulent pathogens, sepsis and lower surgical rates despite more frequent Class I indications for surgery. Prolonged symptom duration was associated with lower cumulative mortality, but this was not significant after multivariable adjustment.